Marcelo Febo, Ph.D.
Department of Psychiatry
University of Florida College of Medicine

“Long-term neural responses to cocaine associated cues”

Abstract

We use neuroimaging methods to study the neural correlates of addiction in rodent models. Presently we are investigating several areas of interest that include: (i) the long term impact of chronic cocaine exposure on the brain dopaminergic system, (ii) the role of brain oxytocin and vasopressin systems in relapse, and (iii) the specific roles of the medial prefrontal cortex and striatum on motivation and emotion. Our work could contribute significantly to understanding conditions such as addiction and depression.

“Neuroscience of Stress and Addiction: Risk, Relapse and Treatment Development”

Abstract

Stress and adversity occurs frequently in society today and are the most common risk factors associated with chronic mental and physical health conditions with the highest public health disease burden. This presentation will focus on the neuroscience of cumulative adversity and stress in humans, with a focus on how stress and adversity related neural changes affects development of depression, anxiety disorders and addiction. Changes in the medial prefrontal brain regulatory systems relating to stress and adversity and to chronic alcohol and drug abuse will be highlighted in the context of the chronic relapsing nature of addictive disorders. Finally, novel therapeutic approaches which address not only the neurobiological changes associated with high stress and trauma, but also craving and relapse risk will be presented. The presentation will conclude with a few provocative points on the role of preventive approaches to address the effects of stress and adversity to decrease chronic psychiatric and physical disease burden.

Yavin Shaham, PhD
Behavioral Neuroscience Branch
NIH/NIDA/IRP

“Incubation of craving and fear: behavioral and neuronal mechanisms”

Abstract

Using a rat model of drug relapse and craving, we previously found time-dependent increases in cue-induced cocaine seeking after withdrawal from the drug, suggesting that cocaine craving incubates over time (Grimm et al. Nature 2001). In this lecture, I will summarize results from studies on the generality of this phenomenon to other drug and non-drug rewards and to fear conditioning in a rat model of incubation of fear. I will then summarize results from a series of studies on the neuronal mechanisms of incubation of drug craving. These include recent studies on the role of Toll-like receptor 4 (an innate immune system pattern recognition receptor) in incubation of heroin craving, and the role of orbitofrontal cortex neuronal ensembles in this incubation.

Bruce T. Hope, Ph.D.

Neurobiology of Relapse Section, NIDA-IRP

“Neuronal ensembles in addiction”

Abstract

Learned associations between drugs and cues in the environment play an important role in drug addiction. Specific patterns of sparsely distributed neurons, called neuronal ensembles, are selectively activated by cues and thought to encode drug-related learned associations. We found neuronal ensembles in rat nucleus accumbens and prefrontal cortex that are selectively activated by contextual cues and play causal roles in several drug-related behaviors. We also found distinct molecular and electrophysiological alterations in these neuronal ensembles that likely mediate the formation and maintenance of learned associations in behaviors related to drug addiction.

Our laboratory uses rodent models to investigate interactions between drug use and decision-making processes. We have found that chronic cocaine self-administration causes long-lasting increases in impulsive and risky choice behavior. In addition, we have found that individual differences in risk taking predict subsequent cocaine self-administration, and that this relationship may be mediated by D2 dopamine receptor expression in the striatum. Considered together, these findings indicate the presence of bi-directional relationships between cocaine use and maladaptive decision-making, which have the potential to further the process of addiction.

Charlotte Boettiger, Ph.D.
Department of Psychology, Biomedical Research Imaging Center
Bowles Center for Alcohol Studies, and Curriculum in Neurobiology
University of North Carolina, Chapel Hill

“Probing the Neurobiology of Cognitive Intermediate Phenotypes of Addictive Disorders”

Abstract

Addictive disorders (SUDs) are highly prevalent and significantly under-treated, due in part to our incomplete understanding of the neurobiological bases of these disorders. We are approaching this issue by investigating the neurobiology of intermediate phenotypes of SUDs that are less etiologically complex and more amenable to biological investigation. One cognitive intermediate phenotype that my lab investigates is the strong tendency to choose smaller, sooner rewards (“Now”) over larger, delayed rewards (“Later”). This “Now bias” can be reliably measured in the lab and reflects a key aspect of SUDs: acting without regard for long-term consequences. While we have much to learn about the biological bases of Now bias in humans, fMRI studies of Now/Later decision-making suggest the importance of frontal regions. Activity in these areas differs based on alcohol use history. In addition to alcohol history, a genetic index of frontal dopamine (DA) levels predicts both Now/Later preference and underlying brain activity; low frontal DA is associated with Now bias in adults. Two biological factors that alter DA signaling, adolescent development and the ovarian cycle, both predictably shift Now bias, which suggests that manipulating DA signaling may effectively change Now bias. Indeed, we find that acute DA reduction significantly increases Now bias in adult males carrying a genetic marker of low frontal DA. Our data support the idea that pharmacological interventions can effectively change Now bias, an approach that holds therapeutic promise for SUDs, but caution that several state factors may substantially impact the outcome of pharmacological interventions.